This proposal builds on the unprecedented success achieved by our earlier studies in safely ablating malignant EMT-6 carcinomas in the thighs of mice by using photoactivation radiosurgery mediated by gold nanoparticles (so-called metal-enhanced radiosurgery [MERS]). MERS will be tested for its safety and efficacy in palliating imminently lethal brain tumors [transgenic v-src malignant gliomas] in mice. As the latter is a neuropathologically documented murine model of human malignant gliomas, it is expected that the proposed study will quickly and economically test the postulate that MERS shows promise to contribute to the palliation of some recurrent human gliomas by greatly decreasing the brain tumor burden, thereby enhancing the effectiveness of adjunct drugs and immunotherapies. Tested positive in mice, positive follow-up tests in rats bearing malignant gliomas and satisfactory normal-tissue tolerance tests in fewer large animals (e.g., dogs) would then enable MERS to be brought to clinical trials. PUBLIC HEALTH RELEVANCE: Malignant brain tumors have poor prognoses and new treatments are needed. Here we present a new treatment using gold nanoparticles that enables image guidance of focused irradiation and even magnification of the dose to malignant brain tumors which, if successful, could significantly improve survival. [unreadable] [unreadable] [unreadable]